In prior years, work on this project has focussed on neuronal factors that may participate in the development of increased blood pressure in spontaneously hypertensive rats (SHR). In vivo experimentation suggested that increased sympathetic activity led to increased protein synthesis in small vessels. In addition, we found that at least in part, the genes for cardiac hypertrophy were independent of the genes for hypertension. In order to investigate these questions at the molecular level, we have established a system for culturing smooth muscle cells from the medial layer of the rat aorta. With these cells we plan to investigate whether cells differ in their response to adrenergic agents. Initially it appeared that cells from genetically hypertensive rats particularly the stroke-prone substrain had a greater proliferation rate than cells from the normotensive control strain. To investigate this phenomenon further, we are examining the effect of adrenergic agents on various parameters of cell function. Cells from the hypertensive strain respond to beta agonist stimulation with a larger accumulation of cAMP within the cell. This is accumulation blocked by beta blockers. Work also continued on the long-term effect of nutritional factors on the incidence of cerebral lesion. In this study it appears that a modest increase in protein concentration in the diet has a protective effect. Recent studies suggest that this effect may be due in part to increased methionine intake, since addition of 1% methionine to diets with a low content of protein results in an apparent doubling of the life expectancy in stroke-prone rats.